Alzheimer's Disease, Dementia
Conditions
Keywords
dementia, magnesium, learning, memory, Alzheimer's disease
Brief summary
The purpose of this study is to examine the effects of supplementing Magnesium L-Threonate in people with mild to moderate dementia. The investigators' goal is to understand whether Magnesium L-Threonate will be associated with improvement in memory and brain function.
Detailed description
Emerging research on the effects of a novel magnesium compound of L-Threonic Acid Magnesium Salt (L-TAMS) containing Vitamins C and D on cognitive performance suggests that supplementation may benefit individuals with Alzheimer's disease (AD). This proof of concept will assess whether supplementation with Magtein (MGT), a constant release formula of Magnesium L-threonate, Vitamin C, and Vitamin D, is associated with changes in regional cerebral metabolism in elderly people with mild to moderate dementia. This is an open-label, two-month trial consisting of 15-20 participants aged 60 and older with mild to moderate dementia. Subjects will receive 1,800 mg/day of MgT-1219 for a total of 60 days. They will be given neurocognitive testing, blood chemistries, and FDG-PET imaging at baseline, 60 days and more testing at 180 days to assess the acute effect of MgT-1219 on hippocampal and PFC-mediated executive function, attention, reasoning, and memory. Blood draws will be conducted prior to treatment initiation to assess kidney and liver function, complete blood count, fasting plasma insulin, and red blood cell magnesium. Our outcome measures include a combination of neuropsychological testing and neuroimaging. These will be employed to measure changes in the degree of cognitive impairment within subjects over time, as well as between subjects in the intervention and control groups. FDG-PET imaging will be used to assess the degree of synaptic activity and density within subjects at different time points in the study. These measures will be supplemented by measures of, sleep quality, daytime sleepiness, depression, and activities of daily living.
Interventions
DIETARY_SUPPLEMENTMagtein
Sponsors
Magceutics, Inc.
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* People of either gender \> 60 years of age. * Subject scores between 16 and 26 on the MMSE * Subject or representative is willing to sign the consent for prior to enrollment into the study and to participate in all aspects of the study. Prospective subject must give verbal assent if unable to sign written consent. * Adequate visual and auditory acuity to allow neuropsychological testing. * Greater than 12 years of educational achievement, or a General Education Development certificate to allow adequate neuropsychological testing, and consistency of sample. * Female subject is surgically sterile, post-menopausal or agrees to use an acceptable method of birth control. * Subject agrees to stop taking any vitamins, minerals, or dietary/herbal supplements he/she is currently taking at least 7 days prior to randomization and agrees to not take any vitamins, minerals or dietary/herbal supplements other than the study product until after study completion.
Exclusion criteria
* Active heart disease * Uncontrolled high blood pressure (≥ 140/90 mmHg) * Renal or hepatic impairment/disease * Type I diabetes * Unstable thyroid disease * Psychiatric disorder (hospitalized in the past year) * History of drug or alcohol abuse. * Immune disorder (such as HIV/AIDS) * TIAs, carotid bruits, or verified lacunes * Significant pulmonary disease * Contraindication for a PET scan including those who have had a stroke or heart attack in the past 6 months, and those unable or unwilling to lie down for 1 hour. * Any medical condition deemed exclusionary by the Principal Investigator (PI) * History of cancer (except localized skin cancer without metastases or in situ cervical cancer) within 5 years prior to screening. * Currently taking any medications that are known to interact with magnesium. * Currently taking antibiotics as the study product may reduce the absorption of antibiotics. A washout period of 2 weeks is allowed. * On an unstable dose of medication (defined as fewer than 90 days at the same dose). * Currently taking any medication deemed exclusionary by PI. * Allergy or sensitivity to any ingredient in the test product. * Evidence of hepatic or renal dysfunction * History of drug or alcohol abuse in the past 12 months. * Pregnant , lactating, or planning to become pregnant during the study period. * Subject has any condition or abnormality that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the study data. * Subject is participating or has participated in another research study within 30 days prior to the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Cognitive Function | Baseline and 6 months | Neurocognitive assessment - Domain-specific composite scores for the four following cognitive areas include: 1a) Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-COG) (min: 0, max: 70, higher = better, units on a scale) 1b) Mini Mental Status Examination (MMSE) (min: 0, max : 30, higher = better, units on a scale) 1c) Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (min: 40, max: 160, higher = better, units on a scale) 1d) Wechsler Adult Intelligence Scale - Fourth edition (WAIS-IV) (min: 85 , max: 115, higher = better, units on a scale) |
| Change From Baseline in Cognitive Function (DKEFS Color-Word Test) | Baseline and 6 months | 1\) Delis-Kaplan Executive Function System Color-Word Test (DKEFS, assesses executive functioning): no minimum or maximum set, higher is worse, total number of errors |
| Change From Baseline in Cognitive Function (DKEFS - Trail 4) | Baseline to 6 months | This is a graphomotor test comprised of 5 conditions. Condition 4 (Number Letter Switching) is a measure of cognitive flexibility |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CMRgl | Baseline to Day 67 | Brain imaging focusing on the following anatomical regions: medial temporal region (including hippocampus and entorhinal cortex), prefrontal cortex, parietotemporal cortex, posterior cingulate cortex. Increases in the summary index sROI have been shown to track AD-related CMRgl declines. We will be focusing on changes in the cerebral metabolic rate for glucose (CMRgl) from baseline to day 67. |
| RBC Magnesium Chemistry | Baseline and 6 months | Magnesium (mg/dl) in red blood cells |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Magtein Subjects Inclusion criteria included adults of either gender \> 60 years of age (women had to be post-menopausal), a diagnosis of probable AD from their physician, a Mini-Mental State Examination (MMSE) between 14 and 24, adequate visual and auditory acuity to allow for neuropsychological testing, at least 12 years of education (or a GED to allow consistency of the sample), and willingness to or having a representative willing to sign the informed consent prior to enrollment into the study (for those subjects unable to sign or understand informed consent, assent to participate in the study was required), and agreeing to discontinue vitamins, minerals, or dietary/herbal supplements for at least 7 days prior to study entry and until after study completion. | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | Magtein Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 17 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 77.0 years STANDARD_DEVIATION 5.86 |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 17 |
| other Total, other adverse events | 0 / 17 |
| serious Total, serious adverse events | 1 / 17 |
Outcome results
Primary
Change From Baseline in Cognitive Function
Neurocognitive assessment - Domain-specific composite scores for the four following cognitive areas include: 1a) Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-COG) (min: 0, max: 70, higher = better, units on a scale) 1b) Mini Mental Status Examination (MMSE) (min: 0, max : 30, higher = better, units on a scale) 1c) Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (min: 40, max: 160, higher = better, units on a scale) 1d) Wechsler Adult Intelligence Scale - Fourth edition (WAIS-IV) (min: 85 , max: 115, higher = better, units on a scale)
Time frame: Baseline and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Magtein Cognitive Data | Change From Baseline in Cognitive Function | ADAS-COG | -0.58 units on a scale | Standard Deviation 7.58 |
| Magtein Cognitive Data | Change From Baseline in Cognitive Function | MMSE | -1.73 units on a scale | Standard Deviation 2.49 |
| Magtein Cognitive Data | Change From Baseline in Cognitive Function | RBANS | -0.36 units on a scale | Standard Deviation 8.83 |
| Magtein Cognitive Data | Change From Baseline in Cognitive Function | WAIS | -0.07 units on a scale | Standard Deviation 1.86 |
Primary
Change From Baseline in Cognitive Function (DKEFS Color-Word Test)
1\) Delis-Kaplan Executive Function System Color-Word Test (DKEFS, assesses executive functioning): no minimum or maximum set, higher is worse, total number of errors
Time frame: Baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Magtein Cognitive Data | Change From Baseline in Cognitive Function (DKEFS Color-Word Test) | 0.8 total number of errors | Standard Deviation 4.23 |
Primary
Change From Baseline in Cognitive Function (DKEFS - Trail 4)
This is a graphomotor test comprised of 5 conditions. Condition 4 (Number Letter Switching) is a measure of cognitive flexibility
Time frame: Baseline to 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Magtein Cognitive Data | Change From Baseline in Cognitive Function (DKEFS - Trail 4) | 23.5 time in seconds | Standard Deviation 88.5 |
Secondary
Change From Baseline in CMRgl
Brain imaging focusing on the following anatomical regions: medial temporal region (including hippocampus and entorhinal cortex), prefrontal cortex, parietotemporal cortex, posterior cingulate cortex. Increases in the summary index sROI have been shown to track AD-related CMRgl declines. We will be focusing on changes in the cerebral metabolic rate for glucose (CMRgl) from baseline to day 67.
Time frame: Baseline to Day 67
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Magtein Cognitive Data | Change From Baseline in CMRgl | 0.0093 mmol·min-1·100 g-1 | Standard Deviation 0.031 |
Secondary
RBC Magnesium Chemistry
Magnesium (mg/dl) in red blood cells
Time frame: Baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Magtein Cognitive Data | RBC Magnesium Chemistry | -0.007 mg/dl | Standard Deviation 1.16 |